Laboratory of RNA Epigenetics, Institute of Molecular Biology (IMB), Mainz, 55128, Germany.
School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Trends Genet. 2017 Jun;33(6):380-390. doi: 10.1016/j.tig.2017.04.003. Epub 2017 May 9.
Modifications in mRNA constitute ancient mechanisms to regulate gene expression post-transcriptionally. N-methyladenosine (mA) is the most prominent mRNA modification, and is installed by a large methyltransferase complex (the mA 'writer'), not only specifically bound by RNA-binding proteins (the mA 'readers'), but also removed by demethylases (the mA 'erasers'). mA mRNA modifications have been linked to regulation at multiple steps in mRNA processing. In analogy to the regulation of gene expression by miRNAs, we propose that the main function of mA is post-transcriptional fine-tuning of gene expression. In contrast to miRNA regulation, which mostly reduces gene expression, we argue that mA provides a fast mean to post-transcriptionally maximize gene expression. Additionally, mA appears to have a second function during developmental transitions by targeting mA-marked transcripts for degradation.
mRNA 的修饰构成了转录后调控基因表达的古老机制。N6-甲基腺苷（m6A）是最主要的 mRNA 修饰，由一个大型甲基转移酶复合物（m6A“书写器”）进行修饰，不仅可以被 RNA 结合蛋白（m6A“阅读器”）特异性结合，还可以被去甲基酶（m6A“橡皮擦”）移除。m6A mRNA 修饰与 mRNA 处理的多个步骤的调控有关。类比于 miRNA 对基因表达的调控，我们提出 m6A 的主要功能是对基因表达进行转录后微调。与 miRNA 调控大多降低基因表达不同，我们认为 m6A 提供了一种快速的方法来最大程度地增加基因表达的转录后调控。此外，m6A 在发育转变期间似乎通过靶向 m6A 标记的转录本进行降解来发挥第二个功能。
